Journal article

Publication year: 2012

Pages: 106-114

Journal: American Journal of Respiratory Cell and Molecular Biology

Volume number: 46

Issue number: 1

ISSN: 1044-1549

DOI Link: https://doi.org/10.1165/rcmb.2011-0171OC

Publisher: American Thoracic Society

Abstract: 
The present study focused on the influence of nicotinic acetylcholine receptors (nAChR) on ion transport processes in mouse tracheal epithelium. RT-PCR experiments revealed expression of the alpha 3, alpha 4, alpha 5, alpha 7, alpha 9, alpha 10, beta 2, and beta 4 nAChR subunits in mouse tracheal epithelium. In Ussing chamber recordings of mouse tracheae, apically applied nicotine (100 mu M) induced a dose-dependent increase of the transepithelial short-circuit current(EC50: 14.6 mu M). The nicotine-induced effect (I-NIC) was attenuated by mecamylamine (25 mu M, apical) and methyllycaconitine (1 mu M, apical). The nAChR agonist 1.1-dimethyl-4-phenylpiperatinium iodide (DMPP) (100 mu M) revealed apical and basolateral location of the receptors. I-NIC was not affected by the sodium channel inhibitor amiloride (10 mu M, apical) or the cystic fibrosis transmembrane conductance regulator inhibitor CFTRinh-172 (20 mu M, apical) but was reduced by the chloride channel inhibitor 5-nitro-2-(3-phenylpropylamino)benzoic acid (100 mu M, apical), the Na+/K+/2Cl(-) cotransporter inhibitor bumetanide (200 mu M, basolateral), the potassium channel inhibitor Ba2+(5mM, basolateral), and 4.4'-diisothiocyanatostilbene-2.2'-disulfonate (100 mu M, apical), indicating a contribution of Ca2+-activated chloride channels and potassium channels. Removal of extracellular Na+ (apical) or Ca2+ (apical) did not influence I-NIC but reduced the DMPP effect. Experiments with the Ca2+-ionophore A23187, a mix of 3-isobutyl-1-methylxanthine and forskolin, or the inositol-1,4,5-triphospate (IP3) receptor inhibitor 2-aminoethyldiphenyl-borinate (75 mM, apical) decreased INIC, indicating a nicotine-mediated increase of intracellular Ca2+ and cAMP levels involving the IP3 signaling pathway. These findings indicate the activity of Ca2+-permeable nAChRs and alternative metabotropic pathways by nAChR activation that mediate Cl- and K+ transport in tracheal epithelium.

Harvard Citation style: Hollenhorst, M., Lips, K., Weitz, A., Krasteva, G., Kummer, W. and Fronius, M. (2012) Evidence for Functional Atypical Nicotinic Receptors That Activate K⁺-Dependent Cl^- Secretion in Mouse Tracheal Epithelium, American Journal of Respiratory Cell and Molecular Biology, 46(1), pp. 106-114. https://doi.org/10.1165/rcmb.2011-0171OC

APA Citation style: Hollenhorst, M., Lips, K., Weitz, A., Krasteva, G., Kummer, W., & Fronius, M. (2012). Evidence for Functional Atypical Nicotinic Receptors That Activate K⁺-Dependent Cl^- Secretion in Mouse Tracheal Epithelium. American Journal of Respiratory Cell and Molecular Biology. 46(1), 106-114. https://doi.org/10.1165/rcmb.2011-0171OC